1,652 results match your criteria epitope mutated


Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses.

Cell 2021 Jun 30. Epub 2021 Jun 30.

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address:

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape convalescent and vaccine-induced antibody responses has renewed focus on the development of broadly protective T-cell-based vaccines. Here, we apply structure-based network analysis and assessments of HLA class I peptide stability to define mutationally constrained CD8 T cell epitopes across the SARS-CoV-2 proteome. Highly networked residues are conserved temporally among circulating variants and sarbecoviruses and disproportionately impair spike pseudotyped lentivirus infectivity when mutated. Read More

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Synthetic Receptors for Sensing Soluble Molecules with Mammalian Cells.

Authors:
Leo Scheller

Methods Mol Biol 2021 ;2312:15-33

Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Synthetic receptors control cell behavior in response to environmental stimuli for applications in basic research and cell therapy. However, the integration of synthetic receptors in unexplored contexts is cumbersome, especially for nonspecialist laboratories. Here, I provide a detailed protocol on how to use receptors of the generalized extracellular molecule sensor (GEMS) platform. Read More

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January 2021

Therapeutic Implications of Germline Testing in Patients With Advanced Cancers.

J Clin Oncol 2021 Jun 16:JCO2003661. Epub 2021 Jun 16.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: Tumor mutational profiling is increasingly performed in patients with advanced cancer. We determined the extent to which germline mutation profiling guides therapy selection in patients with advanced cancer.

Methods: Patients with cancer undergoing tumor genomic profiling were prospectively consented for germline cancer predisposition gene analysis (2015-2019). Read More

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Immunofluorescence studies to dissect the impact of Cockayne syndrome A alterations on the protein interaction and cellular localization.

Authors:
Amr Ghit

J Genet Eng Biotechnol 2021 Jun 16;19(1):88. Epub 2021 Jun 16.

Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.

Background: Cockayne syndrome (CS), which was discovered by Alfred Cockayne nearly 75 years ago, is a rare autosomal recessive disorder characterized by growth failure, neurological dysfunction, premature aging, and other clinical features including microcephaly, ophthalmologic abnormalities, dental caries, and cutaneous photosensitivity. These alterations are caused by mutations in the CSA or CSB genes, both of which are involved in transcription-coupled nucleotide excision repair (TC-NER), the sub-pathway of NER that rapidly removes UV-induced DNA lesions which block the progression of the transcription machinery in the transcribed strand of active genes. Several studies assumed that CSA and CSB genes can play additional roles outside TC-NER, due to the wide variations in type and severity of the CS phenotype and the lack of a clear relationship between genotype and phenotype. Read More

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Identification of Generalized Peptide Regions for Designing Vaccine Effective for All Significant Mutated Strains of SARS-CoV-2.

Comb Chem High Throughput Screen 2021 Jun 1. Epub 2021 Jun 1.

Center for Interdisciplinary Research and Education, Kolkata, India.

Background: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has become a worldwide pandemic and created an utmost crisis across the globe. To mitigate the crisis, the design of vaccines is a crucial solution. The frequent mutation of the virus demands generalized vaccine candidates, which would be effective for all mutated strains at present and for the strains that would evolve due to further new mutations in the virus. Read More

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Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets.

Immunity 2021 06 6;54(6):1290-1303.e7. Epub 2021 May 6.

Department of Medicine, Washington University School of Medicine, St Louis, MO 63130, USA.

Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we used single-cell sequencing to profile SARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-tagged antigen baits, we isolated B cells specific to the SARS-CoV-2 spike, nucleoprotein (NP), open reading frame 8 (ORF8), and endemic human coronavirus (HCoV) spike proteins. Read More

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Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

Cell 2021 05 20;184(11):2955-2972.e25. Epub 2021 May 20.

Duke Human Vaccine Institute, Durham, NC 27710, USA.

Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (V) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Read More

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Specific heparan sulfate modifications stabilize the synaptic organizer MADD-4/Punctin at C. elegans neuromuscular junctions.

Genetics 2021 05 13. Epub 2021 May 13.

Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, Institut NeuroMyoGène, 69008 Lyon, France.

Heparan sulfate proteoglycans contribute to the structural organization of various neurochemical synapses. Depending on the system, their role involves either the core protein or the glycosaminoglycan chains. These linear sugar chains are extensively modified by heparan sulfate modification enzymes, resulting in highly diverse molecules. Read More

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LY-CoV1404 potently neutralizes SARS-CoV-2 variants.

bioRxiv 2021 May 4. Epub 2021 May 4.

LY-CoV1404 is a highly potent, neutralizing, SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody identified from a convalescent COVID-19 patient approximately 60 days after symptom onset. In pseudovirus studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1. Read More

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Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes.

Science 2021 06 4;372(6546):1108-1112. Epub 2021 May 4.

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor binding domain (RBD). In one subject, just four IgG lineages accounted for 93. Read More

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Novel GLP-1/anti-apolipoprotein B bifunctional fusion protein alleviates diabetes and diabetic complications in combination with low-intensity ultrasound.

Life Sci 2021 Aug 29;278:119549. Epub 2021 Apr 29.

Ultrasound Department of The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang Province, China. Electronic address:

Aims: To engineer and screen a novel GLP-1/anti-apolipoprotein B (apoB) bifunctional fusion protein with therapeutic potential on alleviating diabetes and diabetic complication in combination with low-intensity ultrasound.

Main Methods: Anti-apoB antibodies were screened by phage display technology and further fused to mutated GLP-1 (7-37) via light or heavy fusion to generate bifunctional fusion protein (termed aBG). The optimal design of aBG fusion protein was further confirmed by in vitro epitope competition assay and cAMP accumulation assay. Read More

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Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

Division of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.

(1) Background: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is an intractable problem for many clinical oncologists. The mechanisms of resistance to EGFR-TKIs are complex. Long non-coding RNAs (lncRNAs) may play an important role in cancer development and metastasis. Read More

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Neoantigen Cancer Vaccines: Real Opportunity or Another Illusion?

Arch Immunol Ther Exp (Warsz) 2021 Apr 28;69(1):12. Epub 2021 Apr 28.

Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), AP 70228, Ciudad Universitaria, 04510, Mexico, DF, Mexico.

In this communication, we will analyze some important factors and immunological phenomena related to neoantigen cancer vaccines, with particular emphasis on recently published Phase I clinical trials. Several obstacles and issues are addressed that challenge the current paradigm and inquire if neoantigens, which are essentially single-use vaccine candidates, are legitimate targets to induce protective immune responses with regard to the evolving mutational landscape. We also share insights into the striking similarities between cancer and antigenically variable pathogens and suggest that any successful vaccine against either should demonstrate a similar property: efficient induction of a diverse pool of immune cells equipped to prevent immune escape. Read More

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Low-affinity but high-avidity interactions may offer an explanation for IgE-mediated allergen cross-reactivity.

Allergy 2021 Aug 28;76(8):2565-2574. Epub 2021 May 28.

International Immunology Center, Anhui Agricultural University, Anhui, China.

Background: Allergy is a global disease with overall frequencies of >20%. Symptoms vary from irritating local itching to life-threatening systemic anaphylaxis. Even though allergies are allergen-specific, there is a wide range of cross-reactivities (eg apple and latex) that remain largely unexplained. Read More

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TCRMatch: Predicting T-Cell Receptor Specificity Based on Sequence Similarity to Previously Characterized Receptors.

Front Immunol 2021 11;12:640725. Epub 2021 Mar 11.

La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.

The adaptive immune system in vertebrates has evolved to recognize non-self antigens, such as proteins expressed by infectious agents and mutated cancer cells. T cells play an important role in antigen recognition by expressing a diverse repertoire of antigen-specific receptors, which bind epitopes to mount targeted immune responses. Recent advances in high-throughput sequencing have enabled the routine generation of T-cell receptor (TCR) repertoire data. Read More

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Oncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy.

Nat Commun 2021 03 26;12(1):1930. Epub 2021 Mar 26.

Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.

In our clinical trials of oncolytic vesicular stomatitis virus expressing interferon beta (VSV-IFNβ), several patients achieved initial responses followed by aggressive relapse. We show here that VSV-IFNβ-escape tumors predictably express a point-mutated CSDE1 form of the RNA-binding Cold Shock Domain-containing E1 protein, which promotes escape as an inhibitor of VSV replication by disrupting viral transcription. Given time, VSV-IFNβ evolves a compensatory mutation in the P/M Inter-Genic Region which rescues replication in CSDE1 cells. Read More

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Development of a CD8 co-receptor independent T-cell receptor specific for tumor-associated antigen MAGE-A4 for next generation T-cell-based immunotherapy.

J Immunother Cancer 2021 Mar;9(3)

Medigene Immunotherapies GmbH, Planegg-Martinsried, Germany.

Background: The cancer-testis antigen MAGE-A4 is an attractive target for T-cell-based immunotherapy, especially for indications with unmet clinical need like non-small cell lung or triple-negative breast cancer.

Methods: An unbiased CD137-based sorting approach was first used to identify an immunogenic MAGE-A4-derived epitope (GVYDGREHTV) that was properly processed and presented on human leukocyte antigen (HLA)-A2 molecules encoded by the HLA-A*02:01 allele. To isolate high-avidity T cells via subsequent multimer sorting, an in vitro priming approach using HLA-A2-negative donors was conducted to bypass central tolerance to this self-antigen. Read More

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Hematopoietic expression of a chimeric murine-human CALR oncoprotein allows the assessment of anti-CALR antibody immunotherapies in vivo.

Am J Hematol 2021 06 3;96(6):698-707. Epub 2021 May 3.

Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

Myeloproliferative neoplasms (MPNs) are characterized by a pathologic expansion of myeloid lineages. Mutations in JAK2, CALR and MPL genes are known to be three prominent MPN disease drivers. Mutant CALR (mutCALR) is an oncoprotein that interacts with and activates the thrombopoietin receptor (MPL) and represents an attractive target for targeted therapy of CALR mutated MPN. Read More

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Connexin 43 phosphorylation by casein kinase 1 is essential for the cardioprotection by ischemic preconditioning.

Basic Res Cardiol 2021 03 22;116(1):21. Epub 2021 Mar 22.

Institut für Physiologie, Justus-Liebig Universität Gießen, Aulweg 129, 35392, Giessen, Germany.

Myocardial connexin 43 (Cx43) forms gap junctions and hemichannels, and is also present within subsarcolemmal mitochondria. The protein is phosphorylated by several kinases including mitogen-activated protein kinase (MAPK), protein kinase C (PKC), and casein kinase 1 (CK1). A reduction in Cx43 content abrogates myocardial infarct size reduction by ischemic preconditioning (IPC). Read More

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A new reliable and highly specific monoclonal antibody to detect the C-terminal region of silencer of cytokine signaling 1.

Eur J Haematol 2021 Jul 6;107(1):74-80. Epub 2021 May 6.

Institute of Pathology, University Hospital Ulm, Ulm, Germany.

Introduction: SOCS1, a negative regulator of JAK/STAT signaling, is among the most frequently mutated genes in DLBCL and classical Hodgkin lymphoma. The C-terminal SOCS box domain, mediating the degradation of phospho-JAK2, is often affected or even lacking. The analysis of such variants is hampered by the lack of a SOCS1-specific monoclonal antibody recognizing the C-terminus of SOCS1. Read More

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Cartilage Oligomeric Matrix Protein Induced Arthritis-A New Model for Rheumatoid Arthritis in the C57BL/6 Mouse.

Front Immunol 2021 23;12:631249. Epub 2021 Feb 23.

Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.

The most commonly used strains in experimental research, including genetically modified strains, are C57BL/6 mice. However, so far, no reliable model for rheumatoid arthritis is available, mainly due to the restriction by the MHC class II haplotype H-2. Collagen-induced arthritis (CIA) is the most widely used animal model of rheumatoid arthritis, but C57BL/6 strain is resistant to CIA because there is no collagen II peptide associated with H-2. Read More

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February 2021

A Method for User-defined Mutagenesis by Integrating Oligo Pool Synthesis Technology with Nicking Mutagenesis.

Bio Protoc 2020 Aug 5;10(15):e3697. Epub 2020 Aug 5.

Department of Chemical and Biological Engineering, University of Colorado at Boulder, Colorado, USA.

Saturation mutagenesis is a fundamental enabling technology for protein engineering and epitope mapping. Nicking mutagenesis (NM) allows the user to rapidly construct libraries of all possible single mutations in a target protein sequence from plasmid DNA in a one-pot procedure. Briefly, one strand of the plasmid DNA is degraded using a nicking restriction endonuclease and exonuclease treatment. Read More

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K-Ras Peptide Mimotope Induces Antigen Specific Th1 and B-Cell Immune Responses against G12A-Mutated K-Ras Antigen in Balb/c Mice.

Vaccines (Basel) 2021 Feb 26;9(3). Epub 2021 Feb 26.

Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur 56000, Malaysia.

G12A somatic point mutation in adenocarcinomas is categorized clinically as ineligibility criteria for anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies. In this study, a modified G12A-K-ras epitope (139A) with sequence-specific modifications to improve immunogenicity was developed as a potential vaccine against G12A-mutant cancers. Additionally, coupling of the 139A epitope with a tetanus toxoid (TTD) universal T-cell epitope to improve antigenicity was also reported. Read More

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February 2021

Decreased neutralization of SARS-CoV-2 global variants by therapeutic anti-spike protein monoclonal antibodies.

bioRxiv 2021 Feb 19. Epub 2021 Feb 19.

Monoclonal antibodies against the SARS-CoV-2 spike protein, notably, those developed by Regeneron Pharmaceuticals and Eli Lilly and Company have proven to provide protection against severe COVID-19. The emergence of SARS-CoV-2 variants with heavily mutated spike proteins raises the concern that the therapy could become less effective if any of the mutations disrupt epitopes engaged by the antibodies. In this study, we tested monoclonal antibodies REGN10933 and REGN10987 that are used in combination, for their ability to neutralize SARS-CoV-2 variants B. Read More

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February 2021

Variations in Orf3a protein of SARS-CoV-2 alter its structure and function.

Biochem Biophys Rep 2021 Jul 27;26:100933. Epub 2021 Jan 27.

Department of Zoology, Patna University, Patna, Bihar, 800005, India.

Severe acquired respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread worldwide and acquired multiple mutations in its genome. Orf3a, an accessory protein encoded by the genome of SARS-CoV-2, plays a significant role in viral infection and pathogenesis. In the present in-silico study, 15,928 sequences of Orf3a reported worldwide were compared to identify variations in this protein. Read More

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Single chain variable fragment fused to maltose binding protein: a modular nanocarrier platform for the targeted delivery of antitumorals.

Biomater Sci 2021 Mar;9(5):1728-1738

Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, E-18071 Granada, Spain. and Unit of Excellence in Chemistry Applied to Biomedicine and the Environment of the University of Granada, Spain.

The use of the specific binding properties of monoclonal antibody fragments such as single-chain variable fragments (ScFv) for the selective delivery of antitumor therapeutics for cancer cells is attractive due to their smaller size, low immunogenicity, and low-cost production. Although covalent strategies for the preparation of such ScFv-based therapeutic conjugates are prevalent, this approach is not straightforward, as it requires prior chemical activation and/or modification of both the ScFv and the therapeutics for the application of robust chemistries. A non-covalent alternative based on ScFv fused to maltose-binding protein (MBP) acting as a binding adapter is proposed for active targeted delivery. Read More

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Longitudinal analysis of cell-free mutated KRAS and CA 19-9 predicts survival following curative resection of pancreatic cancer.

BMC Cancer 2021 Jan 11;21(1):49. Epub 2021 Jan 11.

Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Freiburg University Medical Center, Freiburg, Germany.

Background: Novel biomarkers and molecular monitoring tools hold potential to improve outcome for patients following resection of pancreatic ductal adenocarcinoma (PDAC). We hypothesized that the combined longitudinal analysis of mutated cell-free plasma KRAS (cfKRAS) and CA 19-9 during adjuvant treatment and follow-up might more accurately predict disease course than hitherto available parameters.

Methods: Between 07/2015 and 10/2018, we collected 134 plasma samples from 25 patients after R0/R1-resection of PDAC during adjuvant chemotherapy and post-treatment surveillance at our institution. Read More

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January 2021

Design of a companion bioinformatic tool to detect the emergence and geographical distribution of SARS-CoV-2 Spike protein genetic variants.

J Transl Med 2020 12 30;18(1):494. Epub 2020 Dec 30.

Biostatistics, Bioinformatics and Clinical Trial Center, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Background: Tracking the genetic variability of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is a crucial challenge. Mainly to identify target sequences in order to generate robust vaccines and neutralizing monoclonal antibodies, but also to track viral genetic temporal and geographic evolution and to mine for variants associated with reduced or increased disease severity. Several online tools and bioinformatic phylogenetic analyses have been released, but the main interest lies in the Spike protein, which is the pivotal element of current vaccine design, and in the Receptor Binding Domain, that accounts for most of the neutralizing the antibody activity. Read More

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December 2020

Design of an epitope-based peptide vaccine against the SARS-CoV-2: a vaccine-informatics approach.

Brief Bioinform 2021 03;22(2):1309-1323

Centre for Interdisciplinary Research in Basic Science, Jamia Millia Islamia University, New Delhi, India.

The recurrent and recent global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has turned into a global concern which has infected more than 42 million people all over the globe, and this number is increasing in hours. Unfortunately, no vaccine or specific treatment is available, which makes it more deadly. A vaccine-informatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. Read More

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